Large Scale Multielectrode Recording and Stimulation of Neural - PowerPoint PPT Presentation

Large Scale Multielectrode Recording and Stimulation of Neural Activity A. Sher 1 , E. J. Chichilnisky 2 , W. Dabrowski 3 , A. A. Grillo 1 , M. Grivich 1 , D. Gunning 4 , P. Hottowy 3 , S. Kachiguine 1 , A. M. Litke 1 , K. Mathieson 4 , D. Petrusca 1 . 1 Santa Cruz Institute for Particle Physics, University of California, Santa Cruz, CA 2 Systems Neurobiology, Salk Institute, La Jolla, CA 3 AGH University of Science and Technology, Kraków, Poland 4 University of Glasgow, Glasgow, UK

in Cell Membrane Potential Action Potential out ref => network of ~100 billion neurons or not… Extracellular Multielectrode recording of neural activity - Simultaneous activity of many neurons - Best spatial resolution: single neuron - Best time resolution: single action potential

System Overview •Hundreds of electrodes and readout channels •Interelectrode distance of tens of microns •Signal amplification (input ~ hundreds of μ V) •Low noise •DAQ system for digitizing and saving the data •Data analysis

Electrode Array Previous state-of-the-art Now 0.93mm Platinum Black 1.92mm 61 Electrodes NERVE Silicon SILICON Nitride NITRIDE Indium Tin INDIUM Oxide TIN OXIDE Glass GLASS 512 Electrodes 60 μ m S. Kachiguine (SCIPP)

Platchip •64 channels; 120 μ m pitch; die size = 3.3 x 7.8 mm 2 •AC coupling: 150 pF •Platinization current: 0-1.2 μ A (controlled by 5 bit DAC) •Stimulation current: 0-150 μ A (controlled by external analog signal with gain set by 5 bit DAC) Connection Output (to Neurochip) to electrode stimulate platinize 64 channels -2.5 V Common external stimulation signal Design by W. Dabrowski et al., Krakow

Neurochip •64 channels; 120 μ m pitch; die size = 4.8 x 7.8 mm 2 •bandpass filter: 80 - 2000 Hz (typical); equivalent rms input noise ~5 μ V (~7 μ V for complete system with saline; signal amplitude range = 50 – 800 μ V) • sampling rate/channel = 20 kHz (typical); multiplexer freq. = 1.3 MHz (typical) input S&H reference output bandpass bandpass preamp amp filter filter Analog 64 channels multiplexer output Design by W. Dabrowski et al., Krakow

512 electrode Readout System 64-channel 64-channel Platchip Neurochip chamber to reference electrode 512-electrode array Fan-in SCIPP •64:1 multiplexing. •Gain: ~1000. •Bandpass: 80Hz – 2kHz. •Input noise: <10 μ V. •DAQ: NI PCI ADC cards; 20kHz sampling of each channel; 15MB/s data rate.

Retina Retina ~100 million photoreceptors ~1 million axons

Retina Dacey, 2004 How is visual information (patterns, color, motion) encoded by different ganglion cell classes? Collaboration with E.J. Chichilnisky Cajal, 1900 (Salk Institute, San Diego)

Retina OFF ON Parasol Parasol OFF ON Midget Midget

Retina Results: E.S. Frechette, A. Sher, M.I. Grivich, D. Petrusca, A.M. Litke, E.J. Chichilnisky, “Fidelity of the ensemble code for visual motion in primate retina,” J Neurophysiol., 94(1), pp. 119-35, 2005 J. Shlens, G.D. Field, J.L. Gauthier, M.I. Grivich, D. Petrusca, A. Sher, A.M. Litke, E.J. Chichilnisky, “The structure of multi-neuron firing patterns in primate retina,” J Neurosci. , 26(32), pp. 8254-66, 2006 Ongoing work: •Characterization of new cell types •Color processing in the retina

Retinal Development How is retinal architecture and its connectivity to the brain formed? •Molecular cues •Activity dependent “wiring” 512 electrode readout system: best tool to •Characterize mouse retina functional properties •Characterize changes of these properties in genetically modified mice First step: Spontaneous activity in the developing mouse retina (“retinal waves”) Collaboration with D. Feldheim (UC Santa Cruz)

Retinal Stimulation Millions of people have photoreceptor degenerative diseases (Retinitis Pigmentosa, Macular Degeneration) Possible solution: electrical stimulation of retinal ganglion cells. Current state-of-the-art: •Human trials •Array of 16 electrodes of ~500 μ m diameter Credit: DOE Dense electrode arrays + Simultaneous stimulation (Platchip) and recording (Neurochip): •For the first time showed that safe and reliable stimulation with <10 μ m diameter electrodes is possible C. Sekirnjak, P. Hottowy, A. Sher, W. Dabrowski, A.M. Litke, E.J. Chichilnisky, “Electrical stimulation of mammalian retinal ganglion cells with multielectrode arrays,” J Neurophysiol. , 95(6), pp. 3311-27, 2006

New Stimulation Chip •Arbitrary stimulation current patterns on all electrodes •Stimulation artifact suppression Pad to Pad to electrode Neurochip Stimulation circuit holding capacitor Stimulation data Ref bus Real-time stimulation data Design by P. Hottowy et al., Krakow

Neural network Activity in brain slices Current 512 electrode readout and future 512 electrode Stimulation systems => Recording of network activity on unprecedented scale: •Detailed characterization of the neural network properties Simultaneous Stimulation and Recording: •Study of neural plasticity through active interaction with the neural network Collaboration with J. Beggs (Indiana University)

Recording of brain neural activity of freely behaving animals Current: •New 64 channel NeuroPlat chip (built-in AC coupling, digitally controlled gain and bandpass) •Digital logic circuitry to set gain and bandpass on power-up, and to provide continuous multiplexer commands •Battery operated •“Spy” FM transmitter and receiver Future: Addition of electrical stimulation with the new StimChip Some applications (and advantages over the existing wired systems): •Study of brain activity in rats (larger scale of movement; 3D; more natural environment; better scales to larger number of electrodes) •Study of navigation system in barn owls (IN FLIGHT) Collaboration with M. Meister (Harvard U.), T. Siapas (Caltech)

Recording of brain neural activity of freely behaving animals Prototype system: •64 channels •20kHz per channel sampling rate •Noise: <15 μ V •FM signal transmission: up to 60m •Weight: 80g •Operation time: 10hours Successfully tested on a rat two weeks ago!

Future Directions: Technology •Develop a stimulation system based on the new Stimchip. (retinal prosthesis, brain slices). •Further develop the in-vivo system, increasing the number of readout channels and adding stimulation capabilities. •519 electrode arrays with larger (120 μ m) spacing. •Continue work on 30 μ m spacing 519 electrode array (K. Mathieson, et al., University of Glasgow). 519 electrodes 30 μ m prototype 30 μ m 120 μ m

Future Directions: Biology and Medicine Ongoing: •Study of new cell types and color processing in primate retina. •Retinal development. •Retinal prosthesis. •Study of network activity in the brain slices. •Study of brain activity in freely-behaving animals Some of the potential: •Wireless recording of brain activity in epilepsy patients •Screening for neural toxicity